The American Diabetes Association 71st Scientific Sessions:

Sulfonylureas and TZDs Show Increased Morbidities Over Other Agents

Two widely used classes of medications for type 2 diabetes show significantly increased morbidities compared to other agents, according to 2 papers presented at the 2011 American Diabetes Association meeting.

One of the studies saw a significantly increased risk of cardiovascular complications in older adults with type 2 diabetes taking sulfonylureas, compared to those taking metformin. The other saw a more than three-fold increased risk of developing diabetic macular edema (DME) in patients taking thiazolidinediones (TZDs) compared to those taking any other medication. Neither study examined the potential for within-class risk variations in the 2 drug classes.

Although not randomized, the risks seen in the large retrospective cohort studies have been previously observed in published papers and warrant consideration by physicians, the first author of the TZD paper said.

“There are lots of case reports and case series describing this association,” said Iskander Idris, DM, FRCP, consultant in diabetes and endocrinology and honorary senior lecturer at the University of Sheffield, England. “The United Kingdom’s drug regulatory agency has put out a warning about the association between TZDs and eye disorders. They included a caveat that while it’s something to be vigilant about, we don’t know for certain if the association is real. Only a randomized trial can settle it for certain.”

His study (abstract 135-OR) used a large UK database to examine 103,368 type 2 diabetes patients without DME at baseline, divided according to whether they received TZDs or not. At one year following baseline, the incidence of DME was 1.3% among TZD users and 0.2% among those receiving other treatments (OR 5.7, 95% CI 4.1 to 7.9). The difference remained significant following adjustment for potential confounders. At 10 years following baseline, and after adjustment, the association still remained significant (HR 2.3, 95% CI 1.8 to 3.0).

Combination therapy of insulin and TZD was found to increase the risk of developing DME even more, while RAS blockade lowered the risk.

“Patients at high risk of sight-threatening DME should avoid TZDs,” the paper concluded, “and the ocular safety of newer PPAR-g agonists merits prospective evaluation.”

Despite that note of caution, Dr. Idris said he still treats selected patients with TZDs when appropriate.

“I would use it in people who have severe insulin resistance or with fatty liver disease,” he said.

The other study (abstract 38-OR) used the GE electronic medical record database to compare 8,502 patients over the age of 65, half of whom were prescribed metformin monotherapy for at least 3 months between 2003 and 2007, and the other half prescribed sulfonylurea monotherapy.

After controlling for potential confounders, patients who initiated with a sulfonylurea had a significantly higher incidence (p<0.001) of experience a coronary vascular event (12.4% vs. 10.4%) compared to those initiated with metformin after 2 years of follow-up.

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